Anterior cruciate ligament (ACL) tears are an extremely common and debilitating injury. ACL reconstruction surgery is successful at improving short-term function. However, long-term outcomes remain sub-optimal with a large majority of patients developing osteoarthritis (OA) at 10-15 year follow-up, which can result in extended periods of pain and disability before joint replacement becomes a feasible option. Thus, there is an urgent need to develop improved treatment options for patients with ACL reconstruction to halt the progression of joint degeneration and thereby improve long-term outcomes. This study will investigate whether altered cartilage contact patterns persist following ACL reconstructive surgery, and then contribute to the pathogenesis of early cartilage degeneration.
The first Aim will establish a new dynamic magnetic resonance (MR) imaging approach for rapidly acquiring three-dimensional (3D) image volumes during knee flexion-extension motion. High resolution models of bone and cartilage morphology will be optimally registered with these dynamic images, allowing for simultaneous analysis of joint motion and inter-segmental cartilage contact.
The second Aim will assess whether abnormal cartilage contact patterns are evident during loaded movement in ACL reconstructed knees. Eighteen patients who underwent ACL reconstructive surgery between 1 and 2 years prior will be bilaterally imaged while performing a knee flexion-extension task within the bore of a 3.0T MR scanner. The data will be used to test the hypothesis that relatively small changes in knee motion can significantly shift the cartilage contact to regions that are less accustomed to compressive loading.
The final Aim will investigate the relationship between cartilage contact and MR parameters of early cartilage degeneration. The 18 subjects with ACL reconstruction in Aim 2 will undergo high resolution morphological and physiological imaging to identify regional changes in cartilage composition and thickness. Cartilage T1-rho and T2 relaxation time and cartilage thickness maps will be compared to cartilage contact maps in the reconstructed and contralateral knees. These data will be used to test the hypothesis that areas of cartilage which are loaded in the reconstructed knee but not the contralateral knee will show the greatest changes in MR biomarkers of cartilage physiology and morphology. Successful completion of this exploratory proposal will establish the MR technology needed to further investigate the pathogenesis of OA in patients with ACL reconstruction while also considering the influence of other potential risk factors including meniscal tears and osteochondral injuries. The innovative approach could also be used to assess the efficacy of alternative surgical treatment options for patients with ACL injury which may better restore joint kinematics and thereby prevent the development of early OA.

Public Health Relevance

Individuals who undergo knee ligament reconstructive surgery are at high risk for developing osteoarthritis (OA) at a relatively young age. This study will develop new imaging technologies to access whether small changes in joint mechanics that persist after surgery contribute to the early onset of OA. The technology and results will provide a scientific basis for evaluating new treatment options that better restore normal knee function and mitigate the potential for OA to occur.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AR062733-02
Application #
8494574
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Lester, Gayle E
Project Start
2012-08-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$157,393
Indirect Cost
$50,518
Name
University of Wisconsin Madison
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Westphal, Christopher J; Schmitz, Anne; Reeder, Scott B et al. (2013) Load-dependent variations in knee kinematics measured with dynamic MRI. J Biomech 46:2045-52